The overall objective of this research proposal is to develop a clear understanding of the membrane mechanisms which regulate intercellular communication in mature, developing and cancerous cells. The studies will be concerned with gap junction ultrastructure; isolation and chemical characterization of junctional protein; correlation between gap junction structure and permeability; structure of gap junctions during cell differentiation and malignant transformation. Various techniques such as thin sectioning, freeze-fracture followed by rotary shadowing, negative staining, optical diffraction and image reconstruction, membrane fractionation, SDS polyacrylamide gel electrophoresis, intracellular recording of electrical coupling etc., will be applied in an attempt to define the molecular architecture of intercellular ionic channels and the structural changes which allow a fine modulation of cell-to-cell communication. Several proposed projects are based on recent evidence for changes in gap junction structure with functional uncoupling (Peracchia and Dulhunty, 1976; Peracchia, 1977).